We compared the power of six different study designs to detect resistance effects for a dichotomous outcome by simulation (Figure 2). Our intent is to mimic sampling strategies that could be used in a typical intervention or prevention trial, with subjects ascertained prior to onset of the outcome and assume a sampling unit of a parent-child trio. We treated a case-control sampling strategy as the reference group (Figure 2a) with a sample of 500 trios with an affected offspring and 500 control trios, irrespective of parental affection status. We examined random sampling of 1000 trios from the population (Figure 2b), where trios where simulated as randomly ascertained from the population with respect to all parameters. We included a low-risk (high resistance) design (Figure 2c). Under the low-risk design, a sample of 1,000 offspring from a larger total population is selected from below the 10tth percentile and above the 60th percentile respectively on a known liability distribution. We examined the power of the high-risk design, where subjects were ascertained through the father, with 500 case fathers and 500 control fathers (Figure
